Protective effects of ONO-3307, a new synthetic protease inhibitor against experimental disseminated intravascular coagulation in rats.
The effects of ONO-3307 (4-sulfamoylphenyl 4-guanidinobenzoate methanesulfonate), a new synthetic protease inhibitor, on endotoxin-induced experimental disseminated intravascular coagulation (DIC) were studied in rats. Experimental DIC was induced by a 4-h sustained infusion of endotoxin at a dose of 100 mg/kg. The rats were infused continuously with ONO-3307 at a dose of 1, 10 or 100 micrograms/kg/h into a femoral vein for 4 h. Simultaneously with the agent infusion, endotoxin (100 mg/kg/4h) was administered into the contralateral femoral vein. A protective effect against DIC was noted in the rats treated with 10 or 100 micrograms/kg/h of ONO-3307 in the following parameters: fibrinogen and fibrin degradation products, fibrinogen level, prothrombin time, partial thromboplastin time, platelet count and the number of renal glomeruli with fibrin thrombi. Therefore, ONO-3307 inhibited the aggravation of endotoxin-induced experimental DIC in rats.
Yoshikawa
T
T
First Department of Medicine, Kyoto Prefectural University of Medicine, Japan.
Takeda
S
S
Naito
Y
Y
Kondo
M
M
D000818:Animals; D004211:Disseminated Intravascular Coagulation / Q000097:blood / Q000139:chemically induced / Q000517:prevention & control*; D004731:Endotoxins / Q000633:toxicity; D005260:Female; D005337:Fibrin / Q000378:metabolism; D005338:Fibrin Fibrinogen Degradation Products / Q000378:metabolism; D005340:Fibrinogen / Q000378:metabolism; D006146:Guanidines / Q000008:administration & dosage / Q000494:pharmacology*; D007678:Kidney Glomerulus / Q000473:pathology; D010314:Partial Thromboplastin Time; D010976:Platelet Count; D011517:Prothrombin Time; D051381:Rats; D011919:Rats, Inbred Strains; D015842:Serine Proteinase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D013927:Thrombosis / Q000473:pathology
D004731:Endotoxins; D005338:Fibrin Fibrinogen Degradation Products; D006146:Guanidines; D015842:Serine Proteinase Inhibitors; C062836:ONO 3307; D005337:Fibrin; D005340:Fibrinogen